Gastrointestinal bleeding is a fairly common medical problem. About 50% of patients suffering from gastric ulcer are diagnosed as hemorrhagic gastric ulcer. In about 80% of the cases, gastrointestinal bleeding mostly occurs in the upper-gastrointestinal tract. In upper-gastrointestinal bleeding, the bleeding originates in the esophagus, stomach, or duodenum, and results in haematemesis and melaena. A bleeding site in upper-gastrointestinal bleeding can be identified by an endoscopic method; and the identification rate thereof is about 90%. Gastric or colonic polypectromies, endoscopic mucosal resections, and endoscopic treatments are variously performed in order to treat gastric or colon cancer. However, during or after such treatments, sometimes bleeding from the stomach or colon occurs, which may require emergency surgical interventions or even lead to death of the patient.
Recently, endoscopic hemostatic methods are being performed in order to treat gastrointestinal bleeding. The endoscopic hemostatic methods include, for example, a direct local-injection of hypertonic saline, epinephrine, or alcohol; a coagulation therapy using electric heat, argon or laser; and a physical hemostatic method using a clip. However, the conventional methods aim at reducing the amount of bleeding, through pressing by injecting a liquid agent into blood vessels around an ulcer or through ligating blood vessels per se. Accordingly, the ulcer remains as its mucous membrane is exfoliated. As a result, even after the treatment, the bleeding often continues. According to research studies, the conventional endoscopic hemostatic treatment is successful in only 70 to 80% of the cases. Further, bleeding reoccurs in 20 to 25% of the cases, 3 to 4 days after the endoscopic hemostatic treatment. Re-bleeding refers to bleeding from a blood vessel, and occurs before the ulcer is completely cured by the regeneration of tissue around the ulcer. Thus, there are limitations difficult to be solved by the conventional endoscopic hemostatic methods that stop bleeding when the mucous membrane of the ulcer is exfoliated. That is, in the conventional endoscopic hemostatic methods, healing rate of the ulcer or the lesion is too slow and re-bleeding frequently occurs. In order to solve the problems, the Korean patent publication no. 10-2006-0040329 has disclosed a hemostatic agent for internal body use and a method of applying the hemostatic agent onto an ulcer inside the human body, in which a coating agent having a polymer-solution form is dispersed and coated onto the ulcer in an endoscopic manner to stop bleeding from the ulcer and minimize the possibility of re-bleeding.
Meanwhile, in order to increase the healing rate of the ulcer or the lesion and minimize the possibility of re-bleeding, a multi-functional formulation that can effectively protect wounds (e.g, ulcer and/or lesion) and prevent adhesion, as well as stop bleeding (i.e., providing hemostasis), is required. That is, there is required a formulation administered (or injected) into the gastrointestinal tract through an endoscopic catheter, thereby protecting wounds, providing hemostasis, and/or preventing adhesion. In order to perform local administration into the gastrointestinal tract, the formulation requires not only having an appropriate viscosity and mucosal adhesiveness (i.e., mucoadhesiveness), but also forming a physical protective shield for providing hemostasis in a target area.
For preventing adhesion in an operational region, formulations having a gel form or a sol-gel form have been developed. However, gel formulations having low-viscosity involve many losses thereof during the application to the upper gastrointestinal tract, which results in restricted formation of the physical protective shield. And, although gel formulations having high-viscosity have an excellent mucoadhesiveness, they have disadvantages, for example requiring a high-pressure ejecting device, involving many losses thereof, etc. Sol-gel formulations refer to a formulation changing from a sol form (e.g., before applying into the body) to a gel form at a certain temperature (e.g., body temperature). However, conventional sol-gel formulations have a very short gelation time, which may lead to forming a gel in a catheter before applying into the body; and still involve many losses thereof during the application.